The conventional method of parenteral administration of a drug to a subject is by injection using a hypodermic syringe. A number of difficulties associated with these syringes have led to attempts to derive more advantageous drug delivery devices. Syringes are not generally advocated for use in self administration by patients because of the dangers of embolisms arising from the introduction of air bubbles into the bloodstream, incorrect dosing, and the accidental infection of third parties after use of the syringe. In any event, syringes cannot be used by children or by many elderly patients, and the use of syringes is very traumatic for the large number of people who are needlephobic to a greater or lesser extent.
In trying to provide improved syringes, a number of inventors have focussed on the provision of a pre-filled syringe or a pre-filled ampoule for use in a syringe, as these devices can be useful in addressing the problems of incorrect dosage or incorrect filling of syringes. Furthermore, some syringes have been provided with expelling means which automatically deliver the drug from the syringe body or ampoule, rather than relying on a conventional syringe mechanism which can be difficult to manipulate in a smooth uniform fashion with one hand. Examples of such devices are the syringe disclosed in U.S. Pat. No. 2,390,246, the ampoule disclosed in U.S. Pat. No. 2,445,477 and the disposable needleless hypodermic injector disclosed in U.S. Pat. No. 3,527,212.
The devices of U.S. Pat. Nos. 2,390,246 and 2,445,477 still require the patient to correctly administer the injection, which may be difficult for some patients, and which some patients may refuse to do because of a fear of needles. Furthermore, each of these documents discloses a very sophisticated and complex mechanical arrangement for activating the expelling means. The devices would, in consequence, be prohibitively difficult and expensive to mass produce and would be prone to failure due to device complexity.
The device of U.S. Pat. No. 3,527,212 eliminates the use of needles and has a construction with fewer parts, but manufacture would still be difficult and expensive as the needleless injection of a drug requires the drug to be provided to the skin at pressures in excess of 400 lb/in.sup.2 (27.5 bar). Thus, the device must be provided with a propellant at such a pressure when it is manufactured, and this pressure must be maintained throughout the shelf life of the device in a compartment which is bounded by a membrane strong enough to withstand the pressure but which is nevertheless easily rupturable by the manual depression of a plunger. Again, it will be appreciated that these requirements lead to a product which is quite difficult and expensive to manufacture.
Needleless devices have their own problems, since their correct use requires a certain degree of dexterity and strength. The device must be held firmly against the skin at the correct angle. Correct delivery of the drug requires it to be propelled at high pressure through the skin, so if the device is held at an incorrect angle or is not held firmly enough, then there is a strong likelihood that the medicament will not pass through the skin but will be dispersed into the air. As needleless injectors are usually quite bulky, the dexterity issue may be far from trivial from many patients.
Another limitation which is associated with each of the devices referred to above is that they can only be used for bolus administration, i.e. the immediate injection of a single entire dose. This is not suitable for all therapies, as it may be preferred in many cases to provide a continuous infusion of a drug both to avoid toxicity problems and to provide improved efficacy. Furthermore, if a drug is provided as a bolus injection, it may be necessary to inject a number of doses per day.
A number of infusion pumps are known, such as those described in U.S. Pat. No. 4,886,499 and our own WO 95/13838. In general, however, infusion pumps are far more sophisticated and complex than syringes or syringe-based injectors, with the result that they are unable to compete commercially with conventional injectors.
The problems associated with complex devices should not be underestimated from a manufacturing point of view. Not only does it become increasingly difficult and expensive to mass-produce a device having large numbers of components, but the reliability of such devices is inherently worse. To illustrate this point, if each component in a production line is tested and found to have, on average, a reliability of 99% (1 failure in every 100), then devices having only 5 components can be predicted to have expected reliability rates of 95% (given by 0.99.sup.5). Devices having 10, 20, and 50 of such components can be expected to have reliability rates of 90%, 82% and 61%, respectively. Evidently the safety implications of increasing device complexity cannot be ignored when considering drug delivery devices in particular.
Therefore, among the objects of the present invention are the provision of a drug delivery device which: is capable of delivering a pre-set dosage of drug to a subject; is suitable for use in self-administration by patients (including young patients and elderly patients); does not require the patient to consciously insert a needle into the skin; has a construction sufficiently simple to enable it to be mass produced at least as cheaply as (and in most cases more cheaply than) prior art bolus injectors described in the documents referred to above and substantially more cheaply than prior art infusion pumps; can provide either a bolus injection or can perform a continuous or controlled infusion; and overcomes the disadvantages associated with the conventional hypodermic syringe. Further objects and advantages of the invention will become apparent from the description given below.